NEW PROCESS FOR THE NITRATION OF AROMATIC COMPOUNDS IN MILD, NON-CORROSIVE CONDITIONS

Abstract: The present invention provides a process for the nitration of aromatic substrates. In one process, an aromatic substrate is reacted with a silicate, optionally modified with a metal nitrate, in the presence of an acid anhydride and an organic solvent, followed by the addition of reduced amounts of nitric acid. Isolation of the nitrated products involves filtration, washing and solvent removal. This process can produce either mono- or polynitrated aromatic compounds depending upon the conditions selected and the aromatic substrate. The present invention also provides related processes for the nitration of strongly activated aromatic substrates using only silicates modified with metal nitrate in the presence of acid anhydrides and an organic solvent. All of these processes provide advantages in yield, cost, and safety over the industrial methods of nitration using mixed acids.

Description: DESCRIPTION NEW PROCESS FOR THE NITRATION OF AROMATIC COMPOUNDS IN MILD, NON-CORROSIVE CONDITIONS This invention describes a new process for nitration of aromatic compounds using silicates, optionally modified with metal nitrates, and reduced amounts of nitric acid under mild, non-corrosive conditions. BACKGROUND OF THE INVENTION By far the most common industrial process for nitration of aromatic compounds is the sulfuric acid catalyzed reaction with nitric acid, also called the mixed acid nitration, which is frequently conducted at high temperatures. More particularly, nitration of deactivated aromatic compounds is carried out in nitric acid-oleum. See, G. Ohla, et al., Nitration: Methods and Mechanisms, VCH, New York, 1989. The use of aggressive sulfo-nitric mixtures and the temperature requirements make such nitration processes costly in terms of capital investment and energy. See, Audley, etal., J. Chem. Soc, Chem. Commun., 1053-1055 (1982) and Seifert, J. Org. Chem., 28:125-129 (1963). Additionally, the use of aggressive sulfo-nitric mixtures and elevated temperatures is particularly hazardous. In view of the above disadvantages and safety considerations, considerable effort has focused on discovering means of carrying out nitration processes under mild, non-corrosive conditions. A procedure for the quantitative nitration of aromatic hydrocarbons using a clay modified with cupric nitrate has been reported. However, this process only gives rise to products of mononitration. No polynitration products are observed. See, Cornelis, etal., Tetrahedron Lett., 29:5657-5660 (1988); Laszlo, etal., Chem. Lett., 1843-1846 (1988) and Laszlo, etal., J. Org. Chem., 52:2407-2410 (1987). While the use by others of metal nitrate impregnated clays can be an advantage when only mononitrated products are desired, the method cannot be applied for the production of polynitrated products such as 1 ,3-dinitrobenzene, dinitrotoluenes, dinitronaphthalenes, dinitro-p-cresol, 12,14-dinitrodehydroabietic acid or nitro musks such as musk xylol, i.e. 5-t-butyl- 1 , 3-dimethyl- -2,4,6-trinitrobenzene. Moreover, application of the above mentioned process to the nitration of unactivated aromatic compounds, such as benzene or other aromatic compounds possessing deactivating substituents, leads to low yields of the mononitration products. The above polynitroaromatic compounds are important intermediates for the production of chemicals with many industrial applications and are used in the preparation of polymers, explosives, dyes, pharmaceuticals, agrochemicals and fragrances. Aromatic diisocyanates, which are commonly used in the production of polymers, are currently produced from the corresponding dinitro compounds which are in turn produced using the aggressive sulfo-nitric mixture. Nitrobenzene is produced by nitration of benzene with mixed acid at 50° to 160°C. 1 ,3-Dinitrobenzene is produced in about 82% yield by subsequent nitration of nitrobenzene with mixed acid at 60-90°C. See, Ullmann' s Encyclopedia of Industrial Chemistry, 5 th Ed., VCH, NY, 1987, Vol. A17, p. 415-418. 2,4-Dinitrotoluene and 2,6-dinitrotoluene are produced directly from toluene with mixed acid as a 80:20 mixture. See, Josef Meissner GmbH & Co., DE 2 921 487 (1979). Both this mixture and the 2,4-dinitrotoluene isolated thereof are intermediates for the manufacture of toluenediisocyanate (TDI), an important raw material for the manufacture of polyurethanes and explosives. See, Ullmann' s Encyclopedia of Industrial Chemistry, 5 th Ed., VCH, NY, 1987, Vol. A17, p. 422; Chadwick, etal., in Kirk-Othmer Encyclopedia of Chemical Technology, 3 rd Ed., Wiley Interscience, NY, 1983, Vol. 23, p. 265. 1 ,5-Dinitronaphthalene, an intermediate in the manufacture of diisocyanates, and 1,8-dinitronaphthalene, which is used in the production of dyes, are obtained by nitration of naphthalene with mixed acid. A mixture of isomers is obtained in which the 1,8-isomer predominates. See, Ullmann ' s Encyclopedia of Industrial Chemistry, 5 th Ed., VCH, NY, 1987, Vol. A17, p. 425. 12, 14-Dinitrodehydroabietic acid, an intermediate in the syntheses of physiologically active derivatives possessing the hydrophenanthrene skeleton, is also of industrial interest, and is also produced by nitration with mixed acid. See, Fieser, et al., J. Am. Chem. Soc, 60:159-170 (1951). Similarly, the nitro musks, such as musk tibetene and musk xylol, which are important commodities in the perfumery industry, are currently produced using the aggressive sulfo-nitric mixture. See, Fuson, et al., J. Org. Chem., 13:587-595 (1947) and Carpenter, et al., J. Org. Chem., 16:586-617 (1951). Nitro derivatives of aromatic heterocycles also find application in several fields such as pharmaceutical chemistry, corrosion inhibition, dye production and agrochemistry. 2-Nitroimidazole (azomycin) possesses antimicrobial activity and is an important intermediate in the preparation of 2-nitroimidazolyl carbamates, potential protozoacides; however, its synthesis is difficult and requires reaction of 2-aminoimidazole sulfate with sodium nitrite in the presence of excess copper sulfate. See Beaman, et al., J. Am. Chem. Soc., 87 : 389-390 (1965). 4-Nitroimidazole is more readily obtained by direct nitration of imidazole with nitric acid. See H. Spaenig et al., BASF, DE 2 208 924 (1972). Furfural is nitrated with nitric acid in acetic anhydride solution at 25-40°C to give 5-nitro-2-furaldehyde diacetate and then used directly for the production of derived drugs. See Sanders et al., Ind. Eng. Chem., 47:358-367 (1955) and Ullmann's Encyclopedia of Industrial Chemistry, 5"ι Ed., VCH, NY, 1987, Vol. A17, p. 452. Thiophene and derivatives are nitrated via mixed acid or via acetyl nitrate processes. See Ullmann's Encyclopedia of Industrial Chemistry, 5 th Ed., VCH, NY, 1987, Vol. A17, p. 452-453. A method for the polynitration of arenes at low temperature has been reported recently. See, Suzuki, et al., J. Chem. Soc., Chem. Commun., 1049-1050 (1991). This method involves nitration with nitrogen dioxide, in the presence of ozone and a catalyst, such as methane sulfonic acid. Application of this method to the synthesis of musk xylol proceeds in 80% yield. However, this process has the disadvantage of using nitrogen dioxide, a highly toxic gas. What is needed in the art is a process to selectively prepare mono- or polynitrated aromatic compounds which provides high yields, is economical in terms of energy requirements and capital investment, is efficient in reducing the number of synthetic steps to prepare a particular compound, mild to the substrate as a whole, minimizes the formation of oxidation products, and safe. Quite surprisingly, the present invention fulfills these and other related needs. SUMMARY OF THE INVENTION The present invention provides new processes for the nitration of aromatic substrates. In one process, an aromatic substrate is reacted with a silicate, optionally modified with a metal nitrate, in the presence of an acid anhydride and an organic solvent, followed by the addition of reduced amounts of nitric acid. Isolation of the nitrated products involves filtration, washing and solvent removal. This process can produce either mono- or polynitrated aromatic compounds depending upon the conditions selected and the nature of the aromatic compound. The present invention also provides related processes for the nitration of strongly activated aromatic substrates using only silicates modified with metal nitrate in the presence of acid anhydrides and an organic solvent. All of these processes provide advantages in yield, cost, and safety over the industrial methods of nitration using mixed acids. DETAILED DESCRIPTION Definitions The terms "aromatic compound" and "aromatic substrate" refer to a group of unsaturated cyclic hydrocarbons containing one or more rings. The rings are typified by benzene which has a 6-carbon ring containing three double bonds. Compounds containing multiple rings may have the rings fused together or linked covalently. Examples of such multiple ring aromatic compounds are naphthalene, biphenyl and anthracene. The terms "aromatic compound" and "aromatic substrate" also refer to those compounds described above which contain heteroatoms, for example, pyridine, quinoline and quinoxaline. Other aromatic compounds include certain 5-membered cyclic compounds such as furan and thiophen, including those containing multiple rings such as benzofuran, benzothiophen and indole. As used herein, the terms " aromatic compound " and "aromatic substrate" also refer to polycyclic compounds wherein at least one ring is an aromatic ring as described above. Additionally, any of the aromatic rings described herein may be optionally substituted with halogen atoms, or other groups such as amine (-NH2), alkyl (-R), hydroxy (-OH), carboxaldehyde (-CHO), alkoxy (-OR) and the like. The term " activated", when used to describe an aromatic compound or substrate, refers to compounds having at least one electron donating substituent such as alkyl (-R) or aryl (-Ar) and the like. Examples of activated aromatic substrates and compounds are toluene, xylene, biphenyl, naphthalene and the like. Within the group of activated aromatic compounds or substrates are those which are "strongly activated". The "strongly activated" aromatic compounds or substrates are those having at least one substituent containing an unshared pair of electrons on the atom connected to the aromatic ring. Such groups include -OH, -OR, -NH2, -NHR, -NR2, -NHCOR, -OCOR or the like. Examples of strongly activated aromatic substrates and compounds are phenol, anisole, cresol, aniline and the like. The term "deactivated", when used to describe an aromatic substrate or compound, refers to compounds having electron withdrawing substituents such as carboxaldehyde (-CHO), nitro (-NO2), carboxylic acid (-COOH), sulfonic acid (-S02H), halogens (-F, -Cl, -Br and -I), cyano (-CN), trifluoromethyl (-CF3) and the like. Examples of deactivated aromatic substrates or compounds are benzonitrile, benzoic acid, benzaldehyde, chloronaphthalene, bromobenzene, and the like. The term "unactivated", when used to describe an aromatic substrate or compound, refers to compounds which are unsubstituted. Examples of such compounds are benzene, naphthalene, phenanthrene, anthracene, and the like. As used herein, the term "acid anhydride" refers to anhydrides of lower carboxylic acids and sulphonic acids such as acetic acid, propionic acid, butanoic acid, trifluoroacetic acid, triflic acid and the like. The anhydrides can be either symmetrical (formed by the condensation of two molecules of the same carboxylic acid) or unsymmetrical (formed by the condensation of two different carboxylic acids). As used herein, numerical ranges are meant to be inclusive of their upper and lower limits. Description of the Invention The present invention provides several new processes tor the nitration of aromatic substrates. The processes can be used for the nitration of a wide variety of aromatic substrates to selectively produce either mononitrated products or polynitrated products depending upon the process, the selection of particular reagents and reaction conditions as described more fully below. Further advantages of these processes include the mild nature of the process when compared with the usual mixed acid nitration processes, advantages in terms of non-corrosive conditions, low energy requirements, minimized oxidatin side products and generally better yields. In many cases the transformations are almost quantitative. Additionally, where isomers can be formed, the more valuable isomer from the industrial standpoint will frequently predominate. For example, nitration of toluene using the process of the present invention produces a mixture of at least 9:1 of 2,4- and 2,6-dinitrotoluene, against 8:2 when using mixed acid. See, Josef Meissner GmbH & Co., DE 2 921 487 (1979). In the case of naphthalene, the yields of 1,5- and 1,8-dinitronaphthalene are similar to those obtained industrially either by direct mixed acid nitration ' of naphthalene, or by nitration of 1-nitronaphthalene. However, the process of the present invention has an advantage that much lower temperatures are used (compare, H. Dressier in Kirk-Othmer Encyclopedia of Chemical Technology, 3 rd Ed., Wiley Interscience, NY, 1981, Vol. 15, p. 724 and H. A. Lubs (Ed.), The Chemistry of Synthetic Dyes and Pigments, ACS Monograph No. 127, Reinhold Publ. Co., NY, 1955, p. 71-73). Moreover, in the mixed acid processes of nitration, the nitrated products can undergo violent oxidative degradation, since nitric acid is a powerful oxidizing agent, especially at high temperatures. This disadvantage is minimized in the process of the present invention since it need not be carried out above room temperature. Another advantage to the present invention is the ability to provide a direct nitration of such aromatic compounds as aniline and phenol. Industrially, nitrophenols are not obtained directly from phenol but must be synthesized indirectly. Thus, 2-chloronitrobenzene must first be prepared, then converted to the corresponding 2-nitrophenol. Similarly, 3-nitrophenol and 4-nitrophenol are prepared from 3-nitroaniline and 4-chloronitrobenzene, respectively, while 2,4-dinitrophenol is produced by hydrolysis of 2,4-dinitrochlorobenzene at 95-100°C. Additionally, the industrial mononitration of cresols is also indirect {e.g., 2-nitro-p-cresol is produced from p-toluidine by diazotization followed by hydrolysis). See Ullmann's Encyclopedia of Industrial Chemistry, 5 th Ed., VCH, NY, 1987, Vol. A17, p. 446-451. A further advantage to the present invention is the ability to provide a direct nitration of heteroaromatic compounds, in some instances without the need for any added nitric acid. For example, nitration of furfural according to one process of the present invention gives directly a high yield of 5-nitro-2-furaldehyde diacetate. Industrially, furfural is nitrated with nitric acid in acetic anhydride solution at 25-40°C to give 5-nitro-2-furaldehyde diacetate, used directly for the production of derived drugs. See Sanders, et al., Ind. Eng. Chem., 47:358-367 (1955) and Ullmann's Encyclopedia of Industrial Chemistry, 5 th Ed., VCH, NY, 1987, Vol. A17, p. 452. In its most general application, the present invention provides a process for the nitration of aromatic compounds using the steps: i) preparing an activated mixture of a silicate, an acid anhydride and an organic solvent; ii) combining the aromatic substrate with the activated mixture to produce a reaction mixture; iii) adding nitric acid to the reaction mixture; and iv) isolating the nitrated aromatic compound from the mixture of step iii). In the present inventive process, the first step is the formation of an activated mixture of a silicate, an acid anhydride and an organic solvent. The silicate used provides an inorganic solid acidic support for reagents which carry out the nitration of the aromatic substrates. These supports typically have extensive specific areas upon which the reagents and substrates are deposited. The precise nature of the silicate is not critical, however silicates such as clays, phyllosilicates and aluminosilicates are preferred. A particularly preferred silicate is montmorillonite clay. In certain preferred embodiments, the silicate is modified with a metal nitrate. The type of metal nitrate and the amount can vary greatly depending upon a particular application. Preferred metal nitrates are aluminum nitrate, bismuth nitrate, cadmium nitrate, cerium nitrate, cobalt nitrate, chromium nitrate, manganese nitrate, iron nitrate, nickel nitrate, zinc nitrate or copper nitrate. More preferred is a silicate modified with copper nitrate. A particularly preferred silicate is montmorillonite clay which is modified with copper nitrate {claycop). The amounts of metal nitrate with which a silicate is modified can be from 30 to 150% by weight, preferably about 100% by weight . The acid anhydrides are typically those which are commercially available and inexpensive. Preferred acid anhydrides are acetic anhydride, proprionic anhydride, trifluoroacetic anhydride and triflic anhydride. Particularly preferred is acetic anhydride. Organic solvents used in the present inventive process can be a hydrocarbon solvent such as hexane or cyclohexane, an ether, or a chlorinated hydrocarbon solvent. Preferred solvents are chlorinated hydrocarbon solvents such as chloroform, carbon tetrachloride, methylene chloride, trichloroethylene, tetrachloroethylene, 1 ,1-dichloroethane and 1,2-dichloropropane, with carbon tetrachloride being particularly preferred. The activated mixture of step i) can be prepared by combining the organic solvent, the acid anhydride and the silicate. The precise order of addition can be varied. In a preferred method, the solvent is first added to the silicate at room temperature followed by addition of the acid anhydride. The resulting mixture is optionally stirred for a period of from about 15 minutes to about 45 minutes. In the second step of the present process, the activated mixture is combined with the aromatic substrate to provide a reaction mixture. The order of addition is not critical, however the addition of the substrate to the activated mixture provides the advantage of "one-pot" preparation. The resulting reaction mixture will typically be stirred for periods of from fifteen minutes to six hours, depending on the degree of nitration desired and the nature of the aromatic substrate. In the third step of the process, nitric acid is added to the reaction mixture. Prior to the addition of nitric acid, the reaction mixture will optionally be cooled to 0°C to 5°C. The addition of nitric acid facilitates the nitration process by increasing both the rate of reaction and the yield of nitrated product. The amounts of nitric acid used will often be determined empirically depending upon the reactivity of the aromatic substrate and whether mono- or polynitration is desired. Dinitration of strongly activated aromatic substrates, such as cresols, will typically require from 0.05 mL to 1.0 mL of nitric acid per millimole of substrate, with from 0.20 mL to 0.40 mL per millimole of substrate being preferred. Dinitration of activated aromatic substrates, such as toluene, will typically use slightly larger amounts of nitric acid, preferably 0.50 mL to 1.5 mL per millimole of substrate. Similar amounts are preferred for the mononitration of deactivated aromatic substrates, such as chlorobenzene. Following the addition of nitric acid, the mixture will typically be stirred for a period of time of from 1 to 6 hours, preferably at room temperature. The precise lenght of time will be determined empirically and will depend upon the substrate and the temperature. Particular methods for determining the precise length of time are well know to those of skill in the art and include monitoring the progress of a reaction by gas chromatography, high performance liquid chromatography or thin layer chromatography, or by coupled techniques such as gas chromatography/mass spectrometry (GC/MS). The process concludes with isolating the nitrated aromatic compound from the reaction mixture. The method of isolation is not critical and can be multistep. In a preferred embodiment, the reaction mixture is filtered and the filtrate cake is washed with solvent. The combined solvent and filter cake washes can be washed with water and dried using any conventional drying agent which is compatible with the particular solvent. Preferred drying agents are sodium sulfate, magnesium sulfate, molecular sieves, and the like. After removing the drying agent from the solution, the solvent is removed by evaporation under reduced pressure to provide the isolated crude nitrated aromatic compound. One of skill in the art can readily appreciate that in some instances the nitrated aromatic compound will crystallize in the filtrate and can be separated in a subsequent filtration. Alternatively, the solution can be concentrated and subjected to chromatography to provide the nitrated aromatic compound. In a preferred embodiment, the present invention provides a process for the nitration of an activated aromatic substrate to produce a dinitrated aromatic compound. This process uses steps i) through iv) as described above, wherein the acid anhydride is acetic anhydride and the silicate is modified with copper nitrate. In another preferred embodiment, the present invention provides a process for the nitration of an activated aromatic substrate to produce a mononitrated aromatic compound. This process uses steps i) through iv) as described above, wherein the acid anhydride is acetic anhydride and the silicate is modified with copper nitrate. In yet another preferred embodiment, the present invention provides a process for the nitration of an unactivated aromatic substrate to produce a dinitrated aromatic compound. This process uses steps i) through iv) as described above, wherein the acid anhydride is acetic anhydride and the silicate is modified with copper nitrate. In still another preferred embodiment, the present invention provides a process for the nitration of an unactivated aromatic substrate to produce a mononitrated aromatic compound. This process uses steps i) through iv) as described above, wherein the acid anhydride is acetic anhydride and the silicate is modified with copper nitrate. In another preferred embodiment, the present invention provides a process for the nitration of a deactivated aromatic substrate to produce a mononitrated aromatic compound. This process uses steps i) through iv) as described above, wherein the acid anhydride is acetic anhydride and the silicate is modified with copper nitrate. One of skill in the art can appreciate that the present inventive process is equally useful in the nitration of aromatic substrates having a combination of activating and deactivating substituents. For example, the dinitration of p-cresol proceeds through an intermediate mononitro-p-cresol which has both activating (-OH, -CH3) and deactivating (-NO2) substituents. In another aspect, the present invention provides a process for the nitration of a strongly activated aromatic substrate using the steps: i) preparing an activated mixture of an acid anhydride, an organic solvent and a silicate modified with copper nitrate; ii) combining the strongly activated aromatic substrate with the activated mixture to produce a reaction mixture for a period of time sufficient to form a nitrated aromatic compound; and iii) isolating the nitrated aromatic compound from the reaction mixture. Preferred silicates, acid anhydrides and solvents, as well as amounts of copper nitrate are as described for the above processes. Additionally, one of skill in the art will recognize that considerations such as the order of addition of reagents, temperature ranges, and methods of isolating the nitrated products are all variable as described above. However, in this process the degree of nitration (mononitration or polynitration) will depend upon the amount of modified clay which is used as well as the length of time the substrate is in contact with the activated mixture. To produce a mononitrated aromatic compound, the preferred amount of modified silicate is 100 to 300 milligrams per millimole of stronlgy activated aromatic substrate. To produce a dinitrated aromatic compound, the preferred amount of modified silicate is 200 to 500 milligrams per millimole of strongly activated aromatic substrate. The period of time which is required to effect the mononitration of a strongly activated aromatic substrate ranges from 30 min to 2 hr, while the length of time to achieve dinitration is typically from 1 to 6 hr. Particular methods for determining the precise length of time are well know to those of skill in the art and include monitoring the progress of a reaction by gas chromatography, high performance liquid chromatography, thin layer chromatography, or GC/MS. The present invention further provides a process for the polynitration of a strongly aromatic substrate by the following steps: i) preparing an activated mixture of a silicate modified with a metal nitrate, an acid anhydride and an organic solvent; ii) combining the strongly activated aromatic substrate with the activated mixture to produce a reaction mixture for a period of time sufficient to form a polynitrated aromatic compound; and iii) isolating the polynitrated aromatic compound from the reaction mixture. In preferred embodiments, the silicate, metal nitrate, acid anhydride, organic solvent, and method of isolating the polynitrated aromatic compounds are as described in foregoing processes. The period of time which is required to effect the polynitration of a strongly activated aromatic substrate will be determined empirically and will depend upon the substrate and the temperature. At higher temperatures, shorter periods of time will be required. For strongly activated aromatic compounds such as p-cresol, a reaction time of about 0.5 to 1.5 hours at room temperature will provide dinitro-p-cresol. Particular methods for determining the precise period of time are well known to those of skill in the art and include monitoring the progress of a reaction by gas chromatography, high performance liquid chromatography, thin layer chromatography or GC/MS. The process of the present invention is illustrated in the following Examples for the production of several mono- and dinitroaromatic compounds as well as the trinitroaromatic musk xylol. EXAMPLES Reagents Reagents and aromatic substrates used in the examples below are available from commercial sources. Silicates such as montmorillonite clay (K 10) are available from Aldrich Chemical Company (Milwaukee, Wisconsin, USA) or from Sud-Chemie AG (Munich, Germany). Silicates modified with metal nitrates can be prepared by literature methods. See, Cornelis and Laszlo, Synthesis, 909-918 (1985); Laszlo and Vandormael, Chem. Lett., 1843-1846 (1988); and Cornelis, et al., Tetrahedron Lett., 29:5657-5660 (1988). Briefly, preparations for clays modified with copper nitrate {claycop) and clays modified with iron nitrate {clayfen) are as follows: Clavcop Montmorillonite clay (K 10, 30 g) is added to a solution of copper(ll) nitrate trihydrate (28 g) in 375 mL of acetone. The resulting suspension is placed on a rotary evaporator and the solvent is removed under reduced pressure with gentle heating (water bath at 50°C). After 30 min, the dry solid crust adhering to the walls of the flask is flaked off and powdered. Evaporation is continued for another 30 min to produce claycop as a light blue, free-flowing powder (58 g). Claycop may be prepared and stored for up to three months prior to use. Clayfen In a manner similar to the procedure used for claycop, iron(lll) nitrate nonahydrate (22.5 g) is dissolved in 375 mL of acetone to form a homogeneous rusty brown solution which then turns into a muddy, light brown suspension. To this suspension is added K 10 clay (30 g) in small amounts with stirring. Solvent is removed as described above to yield K 10 clay-supported iron(lll) nitrate {clayfen) as a yellow, floury powder {ca. 50 g). Clayfen is best prepared immediately prior to use and should not be stored in a closed flask. Conditions Unless otherwise noted all reactions were carried out at room temperature on a 10 mmol scale. Isomers were separated by crystallization, typically from an alcohol such as methanol or ethanol, or by column chromatography on silica gel using mixtures of n-hexane and ethyl acetate as eluant EXAMPLE 1 This example illustrates the preparation of 1 ,3-dinitrobenzene as an example of the dinitration of an unactivated aromatic substrate. Benzene (0.78 g, 10 mmol) was added to a suspension of claycop (4.8 g) in carbon tetrachloride (30 mL) and acetic anhydride (15 mL). After 1.5-2 h, the reaction mixture was cooled in an ice bath and nitric acid (10 mL) was added in small portions. After 1-2 h, the reaction mixture was cooled again and more acid (10 mL) added in small portions. After addition of the nitric acid, the reaction mixture was kept at room temperature for 8 h, then filtered. The filter cake was washed with solvent and the combined organic portions were washed with water and dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to provide 1 ,3-dinitrobenzene in 70% yield, which was identical with a sample from commercial sources. EXAMPLE 2 This example illustrates the preparation of 2,4-dinitrotoluene as an example of the dinitration of an activated aromatic substrate. Toluene (0.92 g, 10 mmol) was added to a suspension of claycop (4.8 g) in carbon tetrachloride (30 mL) and acetic anhydride (15 mL). After 1.5-2 h, the reaction mixture was cooled in an ice bath and nitric acid (10 mL) was added in small portions. After addition of nitric acid, the reaction mixture was kept at room temperature for 4 h, then filtered. The filter cake was washed with solvent and the combined organic portions were washed with water and dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to provide a mixture of crude dinitrotoluenes in 85% overall yield, from which were isolated 2,6-dinitrotoluene (10% of the product mixture) and 2,4-dinitrotoluene (90% of the product mixture), which were identical with commercial samples. EXAMPLE 3 This example illustrates the preparation of 1,8-dinitronaphthalene as an example of the dinitration of an unactivated two f used-ring aromatic substrate. The procedure of Example 2 was followed, using naphthalene. After 3.5 h, the reaction mixture was filtered and the filter cake was washed with solvent. The organic portions were combined, washed with water, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to provide 1,8-dinitronaphthalene (65% yield) and 1,5-dinitronaphthalene (30% yield). Only traces of 1,6-dinitronaphthalene and 1 ,7-dinitronaphthalene were detected by GC/MS analysis. Physical data for the isolated compounds was identical with literature data and those samples from commercial sources. EXAMPLE 4 This example illustrates the preparation of 12,14-dinitrodehydroabietic acid and methyl 12,14-dinitrodehydroabietate as an example of the dinitration of an activated hindered polycyclic aromatic diterpenoid. The procedure of Example 2 was followed, using dehydroabietic acid, isolated from commercial disproportionated rosin or produced by disproportionation of commercial rosin, and methyl dehydroabietate, obtained by methylation of dehydroabietic acid with diazomethane. After 2.5 h, the reaction mixtures were treated as described in Example 2 to provide 12,14-dinitrodehydroabietic acid (85% yield) and methyl 12,14-dinitrodehydroabietate (87% yield), respectively. These products were identical with samples prepared by conventional nitration using mixed acid. EXAMPLE 5 This example illustrates the preparation of musk tibetene as an example of the dinitration of an activated aromatic substrate. The procedure of Example 2 was followed, using 5-t-butyl-1,2,3- -trimethylbenzene. After the addition of nitric acid, the reaction mixture was stirred at room temperature for 2.5 h, then treated as described in Example 2 to provide musk tibetene, i.e. 5-t-butyl-4,6-dinitro-1,2,3-trimethylbenzene (5-t-butyl-dinitro-hemi- mellitene) as crystals (m.p. 135-136°C, 93% yield). Physical data for the isolated compound were identical with literature data. EXAMPLE 6 This example illustrates the preparation of musk xylol as an example of the trinitration of an activated aromatic substrate. 5-t-Butil-1,3-dimethylbenzene (1.62 g, 10 mmol) was added to a suspension of claycop (3.0 g) in carbon tetrachloride (30 mL) and acetic anhydride (15 mL). After 1.5-2 h, the reaction mixture was cooled in an ice bath and nitric acid (10 mL) was added in small portions. After 24 h and addition of nitric acid totaling 35 mL, the reaction mixture was filtered. The filter cake was washed with solvent, and the combined organic portions were washed with water, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to provide musk xylol, i.e. 5-t -butyl- 1,3-dimethyltrinitrobenzene as crystals (m.p. 108-112°C, from ethanol in 82% yield). Physical data for the isolated compound were identical with literature data. EXAMPLE 7 This example illustrates the preparation of mononitrochlorobenzene as an example of the mononitration of a deactivated aromatic substrate. Freshly prepared claycop (4.8 g) was suspended in a mixture of carbon tetrachloride (30 mL) and acetic anhydride (15 mL) and stirred at room temperature for about 45 min. Chlorobenzene (1.12 g, 10 mmol) was added and stirring was continued for 2 hr. The resulting mixture was cooled to 0-5°C and nitric acid (15 mL) was slowly added. After 5-6 hr, the mixture was treated as described in Example 2 to provide a quantitative yield of nitrochlorobenzene as a mixture of isomers {para:ortho:metha, 85:13:2, as determined by GC/MS). Physical data for the isolated compounds were identical with literature data. EXAMPLE 8 This example illustrates the preparation of mononitrobenzaldehyde as an example of the mononitration of a deactivated aromatic substrate, wherein increased amounts of the para-nitro isomer are obtained. Freshly prepared claycop (4.8 g) was suspended in a mixture of carbon tetrachloride (30 mL) and acetic anhydride (15 mL) and stirred at room temperature for about 45 min. Benzaldehyde (1.06 g, 10 mmol) was added and stirring was continued for 2 hr. The resulting mixture was cooled to 0-5°C and nitric acid (10 mL) was slowly added. After 3 hr, the mixture was treated as described in Example 2 to provide a mixture of nitrobenzaldehydes {para:ortho:metha, 27%:26%:41%, as determined by GC/MS) in approximately 90% overall yield. EXAMPLE 9 This example illustrates the mono- and the dinitration of a strongly activated aromatic substrate. Freshly prepared claycop (4.8 g) was suspended in a mixture of carbon tetrachloride (30 mL) and acetic anhydride (15 mL) and stirred at room temperature for about 45 min. Aniline (0.93 g, 10 mmol) was added and stirring was continued. After 5 min, 2-nitroacetanilide had formed (as determined by GC/MS) as a result of acylation of the amino group. The reaction mixture was treated as described in Example 2 to provide 2-nitroacetanilide as yellow crystals (m.p. 98-100°C, from methanol in 90% yield) which was identical with a sample from commercial sources. Addition of nitric acid (2 mL) to the reaction mixture, and treatment of the reaction mixture after 6 h as described in Example 2, provided crude dinitroacetanilide in 85% yield, which was crystallized from methanol to provide 2,4-dinitroacetanilide (yellow crystals, m.p. 120-122°C, 76% yield). Physical data for the isolated compound were identical with literature data. EXAMPLE 10 This example illustrates preparation of 2-nitro-p-cresol as an example of the mononitration of a strongly activated aromatic substrate using reduced amounts of a silicate modified with copper nitrate and in the absence of any added nitric acid. Freshly prepared claycop (2.4 g) was suspended in a mixture of carbon tetrachloride (30 mL) and acetic anhydride (15 mL) and stirred at room temperature for about 45 min. p-Cresol (1.08 g, 10 mmol) was added and stirring was continued at room temperature for 15 min. The resulting mixture was filtered, washed, dried and concentrated in the usual manner to provide 2-nitro-p-cresol in 98% yield, which was isolated by crystallization (m.p. 33-35°C, methanol/ether, 80% yield), identical with a sample from commercial sources. EXAMPLE 11 This example illustrates the preparation of 2,6-dinitro-p-cresol as an example of the dinitration of a strongly activated aromatic substrate using a silicate modified with copper nitrate and in the absence of any added nitric acid. An activated mixture of freshly prepared claycop, carbon tetrachloride and acetic anhydride was prepared as described in Example 7. To the activated mixture was added p-cresol (1.08 g, 10 mmol) and stirring was continued at room temperature for 4 hr. The resulting mixture was filtered, washed, dried and concentrated in the usual manner to provide a 79% yield of 2,6-dinitro-p-cresol (m.p. 77-79°C, from methanol). Similar treatment of o-cresol provided 4,6-dinitro-o-cresol in 58% yield. Physical data for the isolated compounds were identical with those of samples from commercial sources. EXAMPLE 12 This example illustrates preparation 2,6-dinitro-p-cresol as an example of the dinitration of a strongly activated aromatic substrate. Freshly prepared claycop (4.8 g) was suspended in a mixture of carbon tetrachloride (30 mL) and acetic anhydride (15 mL) and stirred at room temperature for about 45 min. p-Cresol (1.08 g, 10 mmol) was added and stirring was continued at room temperature for 15 min. Addition of nitric acid (0.5 mL) to the reaction mixture, and treatment of the reaction mixture after 0.5 hr as described in Example 2, provided 2,6-dinitro-p-cresol in 95% yield, which was isolated by crystallization (m.p. 78°C, methanol/ether, 80% yield), identical with a sample from commercial sources. For o-cresol, 2.5 mL of nitric acid were required to produce 4,6-dinitro-o-cresol in 95% yield. EXAMPLE 13 This example illustrates preparation of mononitroanisoles an example of the mononitration of a strongly activated aromatic substrate using reduced amounts of a silicate modified with copper nitrate and in the absence of any added nitric acid. Freshly prepared claycop (2.4 g) was suspended in a mixture of carbon tetrachloride (30 mL) and acetic anhydride (15 mL) and stirred at room temperature for about 45 min. Anisole (1.08 g, 10 mmol) was added and stirring was continued at room temperature for 15 min. The resulting mixture was filtered, washed, dried and concentrated in the usual manner to provide a mixture of 2-nitro-anisole in 44% yield, and 4-riitro-anisole in 52% yield (as determined by GC/MS), identical to samples from commercial sources. EXAMPLE 14 This example illustrates the mononitration of furfural as an example of the mononitration of a five-membered aromatic heterocycle. An activated mixture of freshly prepared claycop, carbon tetrachloride and acetic anhydride was prepared as described in Example 7. To the activated mixture was added furfural (0.96 g, 10 mmol) and stirring was continued at room temperature for 2 hr. The resulting mixture was filtered, washed, dried and concentrated in the usual manner to provide a 65% yield of mononitrofurfurylidene diacetate (as determined by GC/MS). Addition of nitric acid (3 mL) to the reaction mixture as in Example 2 did not change the composition of the reaction product nor the overall yield. EXAMPLE 15 This example illustrates the mononitration and the dinitration of thiophenecarboxyaldehyde. An activated mixture of freshly prepared claycop, carbon tetrachloride and acetic anhydride was prepared as described in Example 7. To the activated mixture was added thiophenecarboxyaldehyde (1.12 g, 10 mmol) and stirring was continued at room temperature for 2hr. The reaction mixture was filtered, dried and concentrated in the usual manner to provide a 75% yield of mononitrothiophenecarboxyaldehyde diacetate (as determined by MS). Addition of nitric acid (2 mL) to the reaction mixture as in Example 2 provided a quantitative yield of dinitrothiophenecarboxyaldehyde diacetate (as determined by MS). EXAMPLE 16 This example illustrates the mononitration and the dinitration of thiophene. An activated mixture of freshly prepared claycop, carbon tetrachloride and acetic anhydride was prepared as described in Example 7. To the activated mixture was added thiophene (0.84 g, 10 mmol) and stirring was continued at room temperature for 30 min. The reaction mixture was filtered, washed, dried and concentrated in the usual manner to provide a 98% yield of mononitrothiophene (as determined by MS). Addition of nitric acid (5 mL) as in Example 2 provided a 90% yield of dinitrothiophene as 6:4 mixture of isomers (as determined by GC/MS). Although the foregoing invention has been described in some detail by way of illustration and example for purpose of clarity of understanding, it will be obvious that certain changes amd modifications may be practiced within the scope of the appended claims.

Claims: CLAIMS 1. A process for the nitration of an aromatic substrate, comprising the steps; i) preparing an activated mixture of a silicate, an acid anhydride and an organic solvent; ii) combining said aromatic substrate with said activated mixture to produce a reaction mixture; iii) adding nitric acid to said reaction mixture; and iv) isolating said nitrated aromatic compound from said mixture of step iii). 2. A process in accordance with claim 1 wherein said silicate is modified with a metal nitrate selected from the group consisting of aluminum nitrate, bismuth nitrate, cadmium nitrate, cerium nitrate, cobalt nitrate, chromium nitrate, manganese nitrate, iron nitrate, nickel nitrate, zinc nitrate and copper nitrate. 3. A process in accordance with claim 1 wherein said silicate is modified with copper nitrate. 4. A process in accordance with claim 1 wherein said silicate is selected from the group consisting of clay, phyllosilicate, and aluminosilicate. 5. A process in accordance with claim 1 wherein said silicate is montmorillonite clay modified with copper nitrate. 6. A process in accordance with claim 1 wherein said organic solvent is selected from the group consisting of chloroform, carbon tetrachloride, methylene chloride, trichloroethylene, tetrachloroethylene, 1 ,1-dichloroethane and 1 ,2-dichloropropane. 7. A process in accordance with claim 1 wherein said acid anhydride is selected from the group consisting of acetic anhydride, propionic anhydride, trifluoroacetic anhydride and triflic anhydride. 8. A process in accordance with claim 1 wherein said aromatic substrate is an activated aromatic compound, said nitrated aromatic compound is a dinitrated aromatic compound, said acid anhydride is acetic anhydride and said silicate is modified with copper nitrate. 9. A process in accordance with claim 1 wherein said aromatic substrate is an activated aromatic compound, said nitrated aromatic compound is a mononitrated aromatic compound, said acid anhydride is acetic anhydride and said silicate is modified with copper nitrate. 10. A process in accordance with claim 1 wherein said aromatic substrate is an unactivated aromatic compound, said nitrated aromatic compound is a dinitrated aromatic compound, said acid anhydride is acetic anhydride and said silicate is modified with copper nitrate. 11. A process in accordance with claim 1 wherein said aromatic substrate is an unactivated aromatic compound, said nitrated aromatic compound is a mononitrated aromatic compound, said acid anhydride is acetic anhydride and said silicate is modified with copper nitrate. 12. A process in accordance with claim 1 wherein said aromatic substrate is a deactivated aromatic compound, said nitrated aromatic compound is a mononitrated aromatic compound, said acid anhydride is acetic anhydride and said silicate is modified with copper nitrate. 13. A process in accordance with claim 1 wherein said aromatic substrate has both activating and deactivating substituents, said acid anhydride is acetic anhydride and said silicate is modified with copper nitrate. 14. A process for the nitration of a strongly activated aromatic substrate comprising the steps; i) preparing an activated mixture of an acid anhydride, an organic solvent and a silicate modified with copper nitrate; ii) combining said strongly activated aromatic substrate with said activated mixture to produce a reaction mixture for a period of time sufficient to form a nitrated aromatic compound; and iii) isolating said nitrated aromatic compound from said reaction mixture. 15. A process in accordance with claim 14 wherein said silicate modified with copper nitrate is present in an amount of 100 to 300 milligrams per millimole of said aromatic substrate and said nitrated aromatic compound is a mononitrated aromatic compound. 16. A process in accordance with claim 14 wherein said silicate modified with copper nitrate is present in an amount of 200 to 500 milligrams per millimole of said aromatic substrate and said nitrated aromatic compound is a dinitrated aromatic compound. 17. A process for the polynitration of a strongly activated aromatic substrate comprising the steps; i) preparing an activated mixture of an acid anhydride, an organic solvent and a silicate modified with a metal nitrate; ii) combining said strongly activated aromatic substrate with said activated mixture to produce a reaction mixture for a period of time sufficient to form a polynitrated aromatic compound; and iii) isolating said polynitrated aromatic compound from said reaction mixture. 18. A process in accordance with claim 17 wherein said silicate modified with a metal nitrate is montmorillonite clay modified with copper nitrate.

Inventors: CORNELIS ANDRE, LASZLO PIERRE, SILVA GIGANTE CARVALHEIRO BARB, VIDAL DE OLIVEIRA BAPTISTA MAR, CORNELIS, ANDRE, LASZLO, PIERRE, SILVA GIGANTE CARVALHEIRO, BARBARA, MANUELA, VIDAL DE OLIVEIRA BAPTISTA MARCELO CURTO, MARIA, J
Applicants: CORNELIS ANDRE, INST NACIONAL DE ENGENHARIA E, LASZLO PIERRE, SILVA GIGANTE CARVALHEIRO BARB, VIDAL DE OLIVEIRA BAPTISTA MAR, CORNELIS, ANDRE, INSTITUTO NACIONAL DE ENGENHARIA E TECNOLOGIA INDU, LASZLO, PIERRE, SILVA GIGANTE CARVALHEIRO, BARBARA, MANUELA, VIDAL DE OLIVEIRA BAPTISTA MARCELO CURTO, MARIA, J
Application year: 1994
Main classification: C07C201
IPC codes: C07C201, C07C205, C07D307, C07D333